Melanocortins (a variety of different peptide products resulting from post-translational processing of pro-opiomelanocortin) are known to have a broad array of physiological actions. Aside from their well known effects on adrenal cortical function (e.g., by ACTH, adrenocorticotropic hormone), and on melanocytes (e.g., by .alpha.-MSH, melanocyte stimulating hormone), melanocortins have been shown to affect behavior, learning, and memory, control of the cardiovascular system, analgesia, thermoregulation, and the release of other neurohumoral agents including prolactin, luteinizing hormone, and biogenic amines. Peripherally, melanocortins have been identified to have immunomodulatory and neurotrophic properties and to be involved in events surrounding parturition.
The melanocortins mediate their effects through melanocortin receptors (MC-R)--a subfamily of G-protein coupled receptors. Other than the MC1-R which was identified as specific for .alpha.-MSH, and MC2-R which was identified as specific for ACTH, the melanocortin receptors cloned and identified to date (MC3-R, MC4-R, MC5-R) are thought of as "orphan" receptors--i.e., the identity of the native ligand for each receptor remains unidentified, and the physiologic function of each receptor type remains unknown.
The agouti protein is a gene product expressed in mice that is known to be involved in determining coat color, but also thought to play a role in obesity when its normal expression pattern is de-regulated and the protein is ubiquitously expressed. The receptor for agouti has not been identified or cloned; however, it has been observed that agouti antagonizes the MSH-induced activation of two melanocortin receptors.